Disease‐modifying approaches for Parkinson disease

Lewis, Simon J.G.

doi:10.5694/mja17.01135

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…In particular, the administration of monoclonal antibodies provided a decrease in For such reasons, α-syn represents a promising therapeutic target for disease-modifying approaches in PD. Starting from the gene level, where SNCA multiplications increase α-syn production, promising results were obtained with RNA interference, providing a significant decrease in α-syn deposition in murine hippocampal neurons [100]. The major argument lies in the ideal target reduction, considering that a decrease of more than 90% of α-syn expression led to nigrostriatal degeneration [101].…”

Section: Discussionmentioning

confidence: 99%

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

Magistrelli

Contaldi

Comi

2021

Life

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Parkinson’s disease (PD) is a common and progressive neurodegenerative disease, caused by the loss of dopaminergic neurons in the substantia nigra pars compacta in the midbrain, which is clinically characterized by a constellation of motor and non-motor manifestations. The latter include hyposmia, constipation, depression, pain and, in later stages, cognitive decline and dysautonomia. The main pathological features of PD are neuronal loss and consequent accumulation of Lewy bodies (LB) in the surviving neurons. Alpha-synuclein (α-syn) is the main component of LB, and α-syn aggregation and accumulation perpetuate neuronal degeneration. Mutations in the α-syn gene (SNCA) were the first genetic cause of PD to be identified. Generally, patients carrying SNCA mutations present early-onset parkinsonism with severe and early non-motor symptoms, including cognitive decline. Several SNCA polymorphisms were also identified, and some of them showed association with non-motor manifestations. The functional role of these polymorphisms is only partially understood. In this review we explore the contribution of SNCA and its product, α-syn, in predisposing to the non-motor manifestations of PD.

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Section: Discussionmentioning

confidence: 99%

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

Magistrelli

Contaldi

Comi

2021

Life

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“…The list of potential neuroprotective targets in PD would seem to be myriad including oxidative stress, mitochondrial dysfunction, calcium homeostasis, ferroptosis and neuroinflammation [ 1 ] but one area deserving of greater attention would appear to be circadian dysfunction. Whilst there has been an increasing recognition about the potential role of the glymphatic system in the overnight clearance of amyloid in Alzheimer’s Dementia [ 2 ], little consideration has been given to the circadian processes occurring at the level of the cell.…”

Section: Introductionmentioning

confidence: 99%

Targeting sleep and the circadian system as a novel treatment strategy for Parkinson’s disease

Feigl,

Lewis,

Rawashdeh

2023

J Neurol

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There is a growing appreciation of the wide range of sleep–wake disturbances that occur frequently in Parkinson’s disease. These are known to be associated with a range of motor and non-motor symptoms and significantly impact not only on the quality of life of the patient, but also on their bed partner. The underlying causes for fragmented sleep and daytime somnolence are no doubt multifactorial but there is clear evidence for circadian disruption in Parkinson’s disease. This appears to be occurring not only as a result of the neuropathological changes that occur across a distributed neural network, but even down to the cellular level. Such observations indicate that circadian changes may in fact be a driver of neurodegeneration, as well as a cause for some of the sleep–wake symptoms observed in Parkinson’s disease. Thus, efforts are now required to evaluate approaches including the prescription of precision medicine to modulate photoreceptor activation ratios that reflect daylight inputs to the circadian pacemaker, the use of small molecules to target clock genes, the manipulation of orexin pathways that could help restore the circadian system, to offer novel symptomatic and novel disease modifying strategies.

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“…The main clinical manifestations include bradykinesia, myotonia, static tremor, and impaired postural reflexes. Meanwhile, PD patients may also be plagued by insomnia, depressive disorders, astriction, and other non-motor symptoms (7)(8)(9). Both motor and non-motor PD symptoms increasingly worsen as the illness progresses.…”

Section: Introductionmentioning

confidence: 99%

The safety and effectiveness of α-synuclein immunotherapy vs. placebo for the treatment of Parkinson’s disease: a systematic review and meta-analysis

Zhang

Wang

et al. 2022

Ann Palliat Med

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Background: There is no consensus on the efficacy of using α-synuclein as the primary immunotherapy site for Parkinson's disease (PD). The present study sought to investigate the safety and effectiveness of α-synuclein immunotherapy for treating PD. Methods:The databases of CNKI, CBM, Cochrane Library, PubMed, Web of Science, and Embase were searched for randomized controlled trials (RCTs). Cochrane Collaboration's bias assessment tool was used to assess the risk of bias in the included articles, and the included PD patients older than 18 years adopted immunotherapy. Stata 15.0 was employed for statistical analysis.Results: A total of 6 RCTs were eligible for the present study, involving 606 immunotherapy recipients (using alpha-synuclein immunotherapy) and 254 control individuals (placebo). Our meta-analysis found no statistical difference in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score [weighted mean difference (WMD): −0.72, 95% confidence interval (CI): −1.56 to 0.13, P=0.099], adverse event incidence [relative risk (RR): 1.06, 95% CI: 0.98 to 1.15, P=0.150], headache incidence (RR: 0.95, 95% CI: 0.67 to 1.34, P=0.773), and constipation incidence (RR: 1.47, 95% CI: 0.77 to 2.78, P=0.242). However, the infection rate in the immunotherapy group was higher than in the control group (RR: 2.29, 95% CI: 1.40 to 3.74, P=0.003). The above results indicate that immunotherapy is significantly different from placebo in MDS-UPDRS and adverse event incidence, but it can reduce the incidence of infection rate.Conclusions: Existing results showed that α-synuclein immunotherapy had no significant effect on PD. high-quality, multi-center, and large-scale clinical studies are desired to corroborate our findings.

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Disease‐modifying approaches for Parkinson disease

Cited by 4 publications

References 15 publications

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

Targeting sleep and the circadian system as a novel treatment strategy for Parkinson’s disease

The safety and effectiveness of α-synuclein immunotherapy vs. placebo for the treatment of Parkinson’s disease: a systematic review and meta-analysis

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